Head injury is the leading cause of traumatic death. Secondary insults, such as hypoxia or hypotension, significantly increase the morbidity and double the mortality of a given brain injury. Of patients dying of head injury, 66-90% have pathologic evidence of ischemic secondary brain injury. The proposal is based on the hypothesis that ischemic secondary brain injury is caused by local perturbations in the vasoreactivity of pial arterioles resulting in reduced blood flow to the area of the injury. To validate this hypothesis we plan to measure pial arteriolar response to hemorrhage alone, a focal cryogenic brain injury alone, and a combination of cryogenic injury and hemorrhagic shock using the closed cranial window technique in a porcine model. After we have determined and quantified the response of the pial circulation to these insults we will determine the test the vasoreactivity of pial arterioles to acetylcholine in the same model using a similar paradigm. If we determine that the reduced cerebral blood flow seen after injury is due to aberrations in vasoreactivity, it will provide insights into the complex and obscure pathophysiology of ischemic secondary brain injury and may provide the basis for testing novel interventions.